Biology subjects

Pessoa-Pereira, D.

Publications and source records attributed to Pessoa-Pereira, D..

2 recordsLinked to original sources

bioRxiv2025

Tick-borne coinfections modulate CD8+ T cell response and progressive leishmaniosis

Leishmania infantum causes human Visceral Leishmaniasis and Leishmaniosis (CanL) in reservoir host, dogs. As infection progresses to disease in both humans and dogs there is a shift from controlling, Type 1, immunity to a regulatory, exhausted, T cell phenotype. In endemic areas, association between tickborne coinfections (TBC) and Leishmania diagnosis and/or clinical severity has been demonstrated. To identify immune factors correlating with disease progression, we prospectively evaluated a cohort of L. infantum infected dogs from 2019-2022. The cohort was TBC-negative with asymptomatic leishmaniosis at the time of enrollment. We measured TBC serology, anti-Leishmania antigen T cell immunity, CanL serological response, parasitemia, and disease severity to probe how nascent TBC perturbs the immune state. At the conclusion, TBC+ dogs with CanL experienced greater increases in anti-Leishmania antibody reactivity and parasite burden compared to dogs that did not have incident TBC during the study. TBC+ dogs were twice as likely to experience moderate (LeishVet stage 2) or severe/terminal disease (LeishVet stage 3/4). Prolonged exposure to TBC was associated with a shift in Leishmania antigen-induced IFN{gamma}/IL-10 and enhanced CD8 T cell proliferation. Frequency of proliferating CD8 T cells significantly correlated with parasitemia and antibody reactivity. TBC exacerbated parasite burden and immune exhaustion. These findings highlight the need for combined vector control efforts as prevention programs for dogs in Leishmania endemic areas to reduce transmission to humans. Public health education efforts should aim to increase awareness of the connection between TBC and leishmaniosis.

immunology↗

bioRxiv2023

Resident Synovial Macrophages in Synovial Fluid: Implications for Immunoregulation in Infectious and Inflammatory Arthritis

ObjectivesResident synovial macrophages (RSM) provide immune sequestration of the joint space and are likely involved in initiation and perpetuation of the joint-specific immune response. We sought to identify RSM in synovial fluid (SF) and demonstrate migratory ability, in additional to functional changes that may perpetuate a chronic inflammatory response within joint spaces. MethodsWe recruited human patients presenting with undifferentiated arthritis in multiple clinical settings. We used flow cytometry to identify mononuclear cells in peripheral blood and SF. We used a novel transwell migration assay with human ex-vivo synovium obtained intra-operatively to validate flow cytometry findings. We used single cell RNA-sequencing (scRNA-seq) to further identify macrophage/monocyte subsets. ELISA was used to evaluate the bone-resorption potential of SF. ResultsWe were able to identify a rare population of CD14dim, OPG+, ZO-1+ cells consistent with RSM in SF via flow cytometry. These cells were relatively enriched in the SF during infectious processes, but absolutely decreased compared to healthy controls. Similar putative RSM were identified using ex vivo migration assays when MCP-1 and LPS were used as migratory stimulus. scRNA-seq revealed a population consistent with RSM transcriptionally related to CD56+ cytotoxic dendritic cells and IDO+ M2 macrophages. ConclusionWe identified a rare cell population consistent with RSM, indicating these cells are likely migratory and able to initiate or coordinate both acute (septic) or chronic (autoimmune or inflammatory) arthritis. RSM analysis via scRNA-seq indicated these cells are M2 skewed, capable of antigen presentation, and have consistent functions in both septic and inflammatory arthritis.

immunology↗